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Phylogenetic clustering of hepatitis C virus among people who inject drugs in Vancouver, Canada.

ABSTRACT: Little is known about factors associated with hepatitis C virus (HCV) transmission among people who inject drugs (PWID). Phylogenetic clustering and associated factors were evaluated among PWID in Vancouver, Canada. Data were derived from the Vancouver Injection Drug Users Study. Participants who were HCV antibody-positive at enrolment and those with HCV antibody seroconversion during follow-up (1996 to 2012) were tested for HCV RNA and sequenced (Core-E2 region). Phylogenetic trees were inferred using maximum likelihood analysis and clusters were identified using ClusterPicker (90% bootstrap threshold, 0.05 genetic distance threshold). Factors associated with clustering were assessed using logistic regression. Among 655 eligible participants, HCV genotype prevalence was: G1a: 48% (n=313), G1b: 6% (n=41), G2a: 3% (n=20), G2b: 7% (n=46), G3a: 33% (n=213), G4a: <1% (n=4), G6a: 1% (n=8), G6e: <1% (n=1), and unclassifiable: 1% (n=9). The mean age was 36 years, 162 (25%) were female, and 164 (25%) were HIV+. Among 501 participants with HCV G1a and G3a, 31% (n=156) were in a pair/cluster. Factors independently associated with phylogenetic clustering included: age <40 (versus age?40, adjusted odds ratio [AOR]=1.64; 95% confidence interval [CI] 1.03, 2.63), human immunodeficiency virus (HIV) infection (AOR=1.82; 95% CI 1.18, 2.81), HCV seroconversion (AOR=3.05; 95% CI 1.40, 6.66), and recent syringe borrowing (AOR 1.59; 95% CI 1.07, 2.36).In this sample of PWID, one-third demonstrated phylogenetic clustering. Factors independently associated with phylogenetic clustering included younger age, recent HCV seroconversion, prevalent HIV infection, and recent syringe borrowing. Strategies to enhance the delivery of prevention and/or treatment strategies to those with HIV and recent HCV seroconversion should be explored, given an increased likelihood of HCV transmission in these subpopulations.

SUBMITTER: Jacka B

PROVIDER: S-EPMC4211947 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Project description:It is hypothesized that social networks facilitate transmission of the hepatitis C virus (HCV). We tested for association between HCV phylogeny and reported injecting relationships using longitudinal data from a social network design study. People who inject drugs were recruited from street drug markets in Melbourne, Australia. Interviews and blood tests took place three monthly (during 2005-2008), with participants asked to nominate up to five injecting partners at each interview. The HCV core region of individual isolates was then sequenced and phylogenetic trees were constructed. Genetic clusters were identified using bootstrapping (cut-off: 70%). An adjusted Jaccard similarity coefficient was used to measure the association between the reported injecting relationships and relationships defined by clustering in the phylogenetic analysis (statistical significance assessed using the quadratic assignment procedure). 402 participants consented to participate; 244 HCV infections were observed in 238 individuals. 26 genetic clusters were identified, with 2-7 infections per cluster. Newly acquired infection (AOR?=?2.03, 95% CI: 1.04-3.96, p?=?0.037, and HCV genotype 3 (vs. genotype 1, AOR?=?2.72, 95% CI: 1.48-4.99) were independent predictors of being in a cluster. 54% of participants whose infections were part of a cluster in the phylogenetic analysis reported injecting with at least one other participant in that cluster during the study. Overall, 16% of participants who were infected at study entry and 40% of participants with newly acquired infections had molecular evidence of related infections with at least one injecting partner. Likely transmission clusters identified in phylogenetic analysis correlated with reported injecting relationships (adjusted Jaccard coefficient: 0.300; p<0.001). This is the first study to show that HCV phylogeny is associated with the injecting network, highlighting the importance of the injecting network in HCV transmission.

Project description:BACKGROUND:People who inject drugs (PWID) experience elevated rates of premature mortality. Although previous studies have demonstrated the role of supervised injection facilities (SIFs) in reducing various harms associated with injection drug use, including accidental overdose death, the possible impact of SIF use on all-cause mortality is unknown. Therefore, we examined the relationship between frequent SIF use and all-cause mortality among PWID in Vancouver, Canada. METHODS AND FINDINGS:Data were derived from 2 prospective cohort studies of PWID in Vancouver, Canada, between December 2006 and June 2017. Every 6 months, participants completed questionnaires that elicited information regarding sociodemographic characteristics, substance use patterns, social-structural exposures, and use of health services including SIFs. These data were confidentially linked to the provincial vital statistics database to ascertain mortality rates and causes of death. We used multivariable extended Cox regression analyses to estimate the independent association between frequent (i.e., at least weekly) SIF use and all-cause mortality. Of 811 participants, 278 (34.3%) were women, and the median age was 39 years (IQR 33-46) at baseline. In total, 432 (53.3%) participants reported frequent SIF use at baseline, and 379 (46.7%) did not. At baseline, frequent SIF users were on average younger than nonfrequent users, and a higher proportion of frequent SIF users than nonfrequent users were unstably housed, resided in the Downtown Eastside neighbourhood, injected in public, had a recent non-fatal overdose, used prescription opioids at least daily, injected heroin at least daily, injected cocaine at least daily, and injected crystal methamphetamine at least daily. A lower proportion of frequent SIF users than nonfrequent users were HIV positive and enrolled in addiction treatment at baseline. The median duration of follow-up among study participants was 72 months (IQR 24-123). In total, 112 participants (13.8%) died during the study period, yielding a crude mortality rate of 22.7 (95% CI 18.7-27.4) deaths per 1,000 person-years. The median years of potential life lost per death was 34 (IQR 27-42) years. In a time-updated multivariable model, frequent SIF use was inversely associated with risk of all-cause mortality after adjusting for potential confounders, including age, sex, HIV seropositivity, unstable housing, at least daily cocaine injection, public injection, incarceration, enrolment in addiction treatment, and calendar year of interview (adjusted hazard ratio 0.46, 95% CI 0.26-0.80, p = 0.006). The main study limitations are the limited generalizability of findings due to non-random sampling, the potential for reporting biases due to reliance on some self-reported information, and the possibility that residual confounding influenced findings. CONCLUSIONS:We observed a high burden of premature mortality among a community-recruited cohort of PWID. Frequent SIF use was associated with a lower risk of death, independent of relevant confounders. These findings support efforts to enhance access to SIFs as a strategy to reduce mortality among PWID. Further analyses of individual-level data are needed to determine estimates of, and potential causal pathways underlying, associations between SIF use and specific causes of death.

Project description:BackgroundApproximately 1% of adults in Thailand are infected with hepatitis C virus (HCV). New direct-acting antiviral agents achieve sustained virologic responses in >95% of HCV-infected patients and are becoming available in countries around the world. To prepare for new HCV treatment options in Thailand, this study characterized HCV infections among people who inject drugs (PWID) in Bangkok.MethodsThe Bangkok Tenofovir Study (BTS) was a pre-exposure prophylaxis trial conducted among PWID, 2005-2013. Blood specimens were randomly selected from PWID screened for the BTS, to test for anti-HCV antibody and HCV RNA. The HVR1 region was amplified by polymerase chain reaction, using multiplex primer sets with unique identifier sequences; amplification products were pooled in sets of 25; and consensus sequencing was performed to characterize individual HCV genotypes.ResultsThe median age of 3679 participants tested for anti-HCV antibody was 31 years, 3016 (82.0%) were male and 447 (12.2%) were HIV infected. The prevalence of anti-HCV antibody was 44.3%. The adjusted odds of testing positive for anti-HCV antibody were higher in men (adjusted odds ratio [aOR] 3.2, 95% confidence interval [CI] 2.4-4.3), those aged 40 years or older (aOR 2.7, 95% CI 2.1-3.5), those who had more than a primary school education (aOR 1.7, 95% CI 1.4-2.1), and those who tested HIV positive (aOR 5.2, 95% CI 3.7-7.4). HCV RNA was detected in 644 (81.3%) of the 792 anti-HCV antibody-positive specimens, yielding an HCV RNA-positive prevalence of 36.0% (95% CI 33.8-38.2). Among a random sample of 249 of the 644 specimens, 218 could be characterized, and the most common HCV subtypes were 1a (30.3%), 1b (12.8%), 3a (35.8%), 3b (6.9%) and 6n (8.7%).ConclusionThe prevalence of anti-HCV antibody among PWID was 44.3% and more than one third (36.0%) were HCV RNA positive. Genotypes 1, 3 and 6 accounted for all typable infections. As the government of Thailand considers introduction of direct-acting antiviral medications for people with hepatitis C, it will be important to ensure that the medications target these subtypes.

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Phylogenetic clustering of hepatitis C virus among people who inject drugs in Vancouver, Canada.

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